Obexelimab for the Treatment of IgG4-Related Disease.

Glucocorticoid agents are a cornerstone of therapy but are limited by toxic effects, and relapse is common after discontinuation.

糖皮质激素是治疗的基础，但其毒性作用有限，停药后复发很常见。

Obexelimab is a bifunctional monoclonal antibody that inhibits B-cell activity through coengagement of CD19 and FcγRIIb without inducing B-cell depletion.

Obexelimab是一种双功能单克隆抗体，通过共结合CD19和FcγRIIb抑制B细胞活性，而不诱导B细胞耗竭。

Methods

In this phase 3, double-blind, randomized, placebo-controlledtrial, patients with active IgG4-related disease received subcutaneous obexelimab at a dose of 250 mg or placebo once weekly for 52 weeks.

在这项III期、双盲、随机、安慰剂对照试验中，患有活动性IgG4相关疾病的患者每周一次皮下注射250毫克的obexelimab或安慰剂，持续52周。

For patients in both groups, glucocorticoids were tapered in a standardized schedule to discontinuation at week 8.

两组患者均按照标准化计划逐渐减少糖皮质激素的剂量，并在第8周完全停药。

The primary end point was the time to the first flare of IgG4-related disease for which rescue therapy was required, as determined by both the investigator and the independent adjudication committee.

主要终点是需要救援治疗的IgG4相关疾病首次发作的时间，这一时间由研究者和独立裁决委员会共同确定。

Key secondary end points included complete remission at week 52 and the cumulative dose of glucocorticoid rescue therapy through week 52.

关键次要终点包括第52周的完全缓解和第52周内的糖皮质激素救援治疗累积剂量。

Results

From January 2023 through November 2024, a total of 194 patients underwent randomization (with 97 assigned to each group).

从2023年1月至2024年11月，共有194名患者进行了随机分组（每组97人）。

The time to the first disease flare that required rescue therapy was significantly longer with obexelimab than with placebo (hazard ratio, 0.44; 95% confidence interval, 0.28 to 0.71; P<0.001); flares were reported in 26 patients (26.8%) in the obexelimab group and in 53 patients (54.6%) in the placebo group.

与安慰剂相比，接受obexelimab治疗的患者首次疾病发作并需要救援治疗的时间显著更长（风险比，0.44；95%置信区间，0.28至0.71；P<0.001）；obexelimab组有26名患者（26.8%）报告了发作，而安慰剂组有53名患者（54.6%）报告了发作。

Obexelimab showed a significant benefit over placebo with respect to all the key secondary end points, including complete remission (37.1% vs. 19.6%, P = 0.005) and the cumulative dose of glucocorticoid rescue therapy (329.5 mg vs. 929.8 mg, P = 0.004).

与安慰剂相比，obexelimab在所有关键次要终点方面显示出显著优势，包括完全缓解（37.1%对比19.6%，P = 0.005）和糖皮质激素救援治疗的累积剂量（329.5毫克对比929.8毫克，P = 0.004）。

Adverse events included arthralgias (in 19.6% of the patients in the obexelimab group vs. 11.3% of those in the placebo group), hypersensitivity (in 16.5% vs. 11.3%), and diarrhea (in 11.3% vs. 6.2%).

不良事件包括关节痛（obexelimab组患者中有19.6%，而安慰剂组患者中有11.3%），超敏反应（分别为16.5%和11.3%），以及腹泻（分别为11.3%和6.2%）。

Serious adverse events occurred in 10.3% of the patients in the obexelimab group and in 18.6% of those in the placebo group.

obexelimab组中有10.3%的患者发生了严重不良事件，而安慰剂组中有18.6%的患者发生了严重不良事件。

Conclusions

Among patients with active IgG4-related disease, weekly obexelimab treatment led to a significantly lower risk of disease flare and significantly less glucocorticoid exposure than placebo.

在活跃的IgG4相关疾病患者中，每周接受obexelimab治疗比安慰剂显著降低了疾病发作的风险和糖皮质激素的暴露。

(Funded by Zenas BioPharma; INDIGO ClinicalTrials.gov number, NCT05662241.).

该项目由Zenas BioPharma资助；INDIGO ClinicalTrials.gov编号，NCT05662241。